The neurochemical substrate of psychotic reactions may involve an overactivity of certain dopamine systems in the brain. Antipsychotic drugs may be therapeutically effective because of their prominent post-synaptic dopamine receptor blocking activity. Prolactin release from the anterior pituitary is under tonic inhibitory control by a dopaminergic system in the hypothalamus. Antipsychotic drugs interrupt this inhibition by blocking dopamine neurotransmission, and thus they enhance prolactin secretion both in laboratory animals and in human subjects. There is evidence that the prolactin response parallels the absorption and metabolism characteristics of antipsychotic drugs, and that it reflects their relative clinical potencies. The present research is directed toward the elucidation of the prolactin release effect of antipsychotic drugs as an "in vivo bioassay" for these drugs in humans. Comparative dose response curves for different drugs are being developed by fully characterizing the complete prolactin response profile in serum over time following parenteral drug administration. These profiles are being compared with other indices of drug pharmacokinetics and pharmacodynamics including direct measurement of drugs in serum. This latter is being accomplished through the development of radioimmunoassays for these drugs. The ultimate purpose will be the development of a standardized predictive test for clinical responsiveness to these drugs in psychiatric patients.